Injectable chitosan thermogels for sustained and localized delivery of pingyangmycin in vascular malformations

Int J Pharm. 2014 Dec 10;476(1-2):232-40. doi: 10.1016/j.ijpharm.2014.09.058. Epub 2014 Oct 3.

Abstract

Pingyangmycin (PYM) is an effective drug to treat vascular malformations (VM), but can easily diffuse from the injection site, which will reduce its therapeutic effect and increase side effect. Our study was to evaluate PYM-loaded chitosan thermogels for sustained and localized embolization therapy. It was shown that in vitro release of PYM thermogels could be delayed up to 12 days. The results measured by MTT assay showed that PYM thermogels could inhibit proliferation and induce apoptosis of EA.hy926 cells in a concentration and time dependent manner. In vivo pharmacokinetics study demonstrated that compared with PYM injections, PYM thermogels had a better sustained delivery of PYM. Macroscopic observation and histological examination of rabbit ear veins displayed that after administration with PYM thermogels for 18 days, obvious venous embolization and inflammatory response could be found. These results indicate that PYM thermogels is likely to achieve excellent prospects for VM treatment.

Keywords: Chemoembolization; Chitosan; Pingyangmycin; Thermogels; Vascular malformations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Bleomycin / administration & dosage
  • Bleomycin / analogs & derivatives*
  • Bleomycin / pharmacokinetics
  • Bleomycin / pharmacology
  • Cell Line
  • Cell Proliferation / drug effects
  • Chitosan / chemistry*
  • Delayed-Action Preparations
  • Drug Delivery Systems*
  • Endothelial Cells / drug effects
  • Female
  • Gels
  • Humans
  • Male
  • Rabbits
  • Time Factors
  • Vascular Malformations / drug therapy*

Substances

  • Delayed-Action Preparations
  • Gels
  • Bleomycin
  • bleomycetin
  • Chitosan